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Low glutathione: amino acids or methylation?

Dreambirdie

work in progress
Messages
5,569
Location
N. California
Has anyone here tried the liposomal glutathione? I am wondering if it would be as helpful as the Lee Silsby's transdermal glutathione...?
 
Messages
39
Location
Bay Area, CA
I usually take 2 600 mg tablets (the Jarrow sustain) for mild toxicity, but have taken as much 3600 mg/day during times when I have a major heavy metal clearing going on. I find it can be a little harsh on my stomach, but it works well to help my liver clear toxins. IN fact sometimes it has been the only thing that has helped me.

Thanks Dreambirdie. Those dosages are in line with what I was seeing in clinical trials (all of which had a very favorable outcome for NAC use ranging from detoxification to neurotoxicity protection to mental health issues). I know I have some mercury built up from a lack of glutathione being able to shepherd it out. Fortunately (if there is a fortunate side to mercury build up!), it's from eating fish in my case, so at least I can easily control the source.

So your only side effects from the NAC have been stomach problems?
 

Valentijn

Senior Member
Messages
15,786
But, in the meantime, is there a dosage that you guys use while on the b12 protocol? (If you are using NAC; I realize it's not a required supp but I think it might help in my case since my cysteine is on the lower end.)

There's several studies where NAC was used with HIV patients to raise glutathione. I based my dosage off of what was safe and effective in those studies. This seems to range between 1800mg/day and a higher amount based on body weight. It's been working well for me at 1800mg/day, so I haven't bothered raising it as high as I could (over 3000mg/day for my weight).

It shouldn't all be taken at once, but spread out throughout the day. I take my last dose right before bed time, to help with sleeping/wired-but-tired problems. It doesn't make me sleepy, but it stops my mind from buzzing all night.
 

Dreambirdie

work in progress
Messages
5,569
Location
N. California
Thanks Dreambirdie. Those dosages are in line with what I was seeing in clinical trials (all of which had a very favorable outcome for NAC use ranging from detoxification to neurotoxicity protection to mental health issues). I know I have some mercury built up from a lack of glutathione being able to shepherd it out. Fortunately (if there is a fortunate side to mercury build up!), it's from eating fish in my case, so at least I can easily control the source.

So your only side effects from the NAC have been stomach problems?

Hi lolasana--

I usually take one 600 mg capsule of NAC in the morning before breakfast and one at night about an hour before bed. If I am feeling very toxic, I will double those doses and possibly add a third dose in the mid day.

What I have found is that if I take the NAC right before bed, I often get heartburn from it, which can last several hours. So in my case, it works best to let it digest a bit before I lay down. That's the only problem I have had with it.

And regarding the fish, I remember recently hearing (or maybe reading?) a report that people in cultures who eat a lot of fish have tested much higher for mercury toxicity. That makes sense to me. Unfortunately, the oceans have become a dumping ground for a lot of toxins and plastic, and now after the Fukushima disaster, nuclear waste. Very awful to think what that will do to all the sea life.
 
Messages
39
Location
Bay Area, CA
Thanks Valentijn and Dreambirdie. I took 600mg NAC about 30 min. before bed last night and it seemed fine.

I was a "pescatarian" for about a year after ending my 14 year vegetarian stint, so fish and eggs were my only sources of animal protein during that time. I ate fish daily and didn't pay much attention to mercury content. A mercury hair test taken before this period of time revealed very little mercury. A year after eating fish with impunity, this level had more than doubled. I am now far more conscientious about the fish I eat; I try to eat only low mercury fish and only eat it 2-3 meals/week. Unfortunately, my body is having a very tough time excreting the mercury that built up during my fish free-for-all. From what I understand, the body uses glutathione to detox/excrete mercury and that is something that I am low on (according to my NutrEval results).

So I'll keep trying the NAC along with the SMP supplements.
 

richvank

Senior Member
Messages
2,732
Hi, lolasana.

In response to your PM request some time ago, I did review your NutrEval panel results, and I also read all your previous posts to PR.

It looks to me as though methylmercury toxicity is a major factor in your case. If you look at the Krebs cycle diagram in your NutrEval results, and note where mercury is shown in the round red boxes, I think that you will see that mercury toxicity can account for several of the bottlenecks in your energy metabolism. Mercury is also elevated in your red blood cells, and some of the essential minerals that are normally carried by metallothionein are depleted, which can be caused by mercury toxicity.

Your glutathione deficiency is consistent with mercury toxicity, also.

You do appear to have a partial methylation cycle block as well, and I'm glad that you are doing a methylation treatment.

I have some concern about your taking NAC, given what appears to be a high burden of methyl mercury in your body. NAC can move methyl mercury from the kidneys into the brain. I suggest that you read David Quig's paper: http://www.altmedrev.com/publications/3/4/262.pdf

I don't know if you will be able to get the upper hand on the methylmercury toxicity by means of the methylation treatment alone, but I hope you will. (As I think you know, mercury can block many of the enzymes the function of which is needed by this part of the metabolism.) If not, you may have to address the mercury issue directly, using a chelation protocol. Andy Cutler's protocol seems to have helped quite a few people, though I haven't agreed with him historically on everything he has posted over the years.

For what it's worth, over the past few years I have encountered quite a few cases of ME/CFS in vegetarians (who often don't get much B12 in their diets) and pescatarians (who get a lot of methylmercury in theirs). It would be interesting to see a study of this, to see if these correlations are statistically significant. I know that many people have strong feelings about this, but from the standpoint of avoiding ME/CFS, I think it is best to avoid these types of diets.

Your selenium is high, and that may be a result of ocean fish being high in both mercury and selenium, given that you have had a high-fish diet.

Best regards,

Rich
 
Messages
39
Location
Bay Area, CA
Thank you Rich, I really appreciate your insight. This has given me a lot to think about.

I recently had a whole blood test that revealed a mercury level of 4.2 (apparently the national average on this test is 0.8). My doctor has recommended a "gentle" detox for the mercury. I have a follow up appointment with her to see what she proposes. I've read a little bit about Cutler's protocol, but I find reading about mercury toxicity especially frightening so I've been hesitant to do a lot of research in that area.

Thanks again.
 

aquariusgirl

Senior Member
Messages
1,732
Returning to the amino acid subject. I just ran a UAA, a couple of days or maybe a day after getting an amino acid IV. Unfortunately, taurine, glycine, glutamate, ammonia ...are elevated, everything else is in the tank.
So now I'm wondering if these IVs are helping or harming.
Or maybe I just need to keep an eye out for ammonia syptoms....I guess everything is a trade off.
 

topaz

Senior Member
Messages
149
Hi, lolasana.

Yes, if the amino acids are too low, the cells will not be able to make glutathione. Normally, the rate-limiting amino acid for making glutathione is cysteine, but if one of others gets too low, it will become rate-limiting.

Amino acids are often found to be low in PWMEs. This can be caused by a low-protein diet, by poor digestion of proteins and absorption of amino acids by the gut, or by excessive burning of amino acids for fuel, because the burning of carbs and fats is limited in ME/CFS by a partial block early in the Krebs cycle at aconitase. Also, I think because of the last-mentioned issue, many PWMEs go low in B6 (or its active form P5P) because of heavy use by the transamination reactions. These are needed to convert one amino acid into another to feed them into the Krebs cycle, so when it goes low, there will be high and low levels of various amino acids, and it becomes difficult to feed them into the Krebs cycle for fuel. This then makes the person more fatigued.

There are free form amino acids supplements, and supplementing B-complex vitamins can also help, if they are low.

Best regards,

Rich

Thank you Rich

I continue to be confused by glutamine, glutamate and ultimately glutathione.

Firstly, glutathione - I agree that the best way to tackle this is to address the cause of low production via methylation. No confusion there.

You say "This can be caused by a low-protein diet, by poor digestion of proteins and absorption of amino acids by the gut, or by excessive burning of amino acids for fuel, because the burning of carbs and fats is limited in ME/CFS by a partial block early in the Krebs cycle at aconitase. "

In my case, I have a relatively high protein diet (read low carb) but show signs of poor protein digestion (via stool analysis). To tackle this, I will undertake the stomach acid test as this has a flow on effect to overall GI health. The immune system predominantly originates in the gut and it appears that tackling the gut and methylation go hand in hand (two legs of a three legged stool).

Having said and agreeing with all that, where I get confused is that I have read in a number of sources that glutamine is the principle metabolic fuel for the intestinal mucosa, or, more specifically, for the cells that line the intestinal epithelium (enterocytes). For this reason, the small and large intestines require more glutamine than any other organ. So long story short, to help restore GI health, glutamine is required (part of the vicious cylce).

Is supplementing with glutamine the same as supplementing with glutathione (I know it is a precursor but dont know how readily it is converted) or would supplementing with glutamine provided the body with the glutamine it needs without necessarily then producing glutathione, which we would prefer to be directly restarted via mehtylation? Or will methylation kick start glutamine production and in turn ultimately glutathione?

I have also read of the dangers of glutamine converting to glutamate and the problems that excess glutamate creates for some.

It really is a vicious cycle - perhaps not surprising given a number of bio chemical processes are imbalanced with CFS.

I worry that my question makes little sense at present as I have experienced a six week brain fog crash (after starting the AMP and possibly over stimulation methylation - cessation of same for over 2 weeks has not helped!). Essentially, I am asking is there a difference between supplementing with glutamine and supplementing with glutathione (not preferred), knowing that glutamine is a precursor?

Deep thanks, as always, for your considered opinions and time.
 

richvank

Senior Member
Messages
2,732
***Hi, topaz.

Thank you Rich

***You're welcome.

I continue to be confused by glutamine, glutamate and ultimately glutathione.

Firstly, glutathione - I agree that the best way to tackle this is to address the cause of low production via methylation. No confusion there.

***O.K.

You say "This can be caused by a low-protein diet, by poor digestion of proteins and absorption of amino acids by the gut, or by excessive burning of amino acids for fuel, because the burning of carbs and fats is limited in ME/CFS by a partial block early in the Krebs cycle at aconitase. "

In my case, I have a relatively high protein diet (read low carb) but show signs of poor protein digestion (via stool analysis). To tackle this, I will undertake the stomach acid test as this has a flow on effect to overall GI health. The immune system predominantly originates in the gut and it appears that tackling the gut and methylation go hand in hand (two legs of a three legged stool).

***O.K. I agree with you.

Having said and agreeing with all that, where I get confused is that I have read in a number of sources that glutamine is the principle metabolic fuel for the intestinal mucosa, or, more specifically, for the cells that line the intestinal epithelium (enterocytes). For this reason, the small and large intestines require more glutamine than any other organ. So long story short, to help restore GI health, glutamine is required (part of the vicious cylce).

***Yes, the cells of the gut do have a big need for glutamine.

Is supplementing with glutamine the same as supplementing with glutathione (I know it is a precursor but dont know how readily it is converted) or would supplementing with glutamine provided the body with the glutamine it needs without necessarily then producing glutathione, which we would prefer to be directly restarted via mehtylation? Or will methylation kick start glutamine production and in turn ultimately glutathione?

***Glutamine and glutamate can be converted one to the other by the enzymes glutaminase and glutamine synthase, respectively. Glutamate is one of the three prescursor amino acids needed to make glutathione, the other two being glycine and cysteine. Usually cysteine is the rate-limiting amino acid for making glutathione, but I have seen cases in which glycine has gone low enough that it becomes rate-limiting. I don't think I've seen cases in which glutamate is rate-limiting, so I don't think that supplementing with glutamine or glutamate will affect the synthesis of glutathione.

***Fixing the methylation cycle will restore the normal ability to convert some of the methionine into cysteine, and that will usually boost the synthesis of glutathione, because cysteine is usually rate-limiting.

I have also read of the dangers of glutamine converting to glutamate and the problems that excess glutamate creates for some.

***Yes, that can be a problem for some people. Too much glutamate in the neuronal synapses in the brain will cause overstimulation of the NMDA receptors, leading to excitotoxicity, with the symptoms of anxiety, nervousness, a "wired" feeling, insomnia, and oversensitivity of the senses.

It really is a vicious cycle - perhaps not surprising given a number of bio chemical processes are imbalanced with CFS.

***Right. It is fairly involved, and there are differences from one person to another, which makes it even more "interesting."

I worry that my question makes little sense at present as I have experienced a six week brain fog crash (after starting the AMP and possibly over stimulation methylation - cessation of same for over 2 weeks has not helped!). Essentially, I am asking is there a difference between supplementing with glutamine and supplementing with glutathione (not preferred), knowing that glutamine is a precursor?

***Hopefully I have addressed your question. Basically, supplementing glutamine would probably help the gut, but unfortunately in some people with ME/CFS, it is not so good for the brain. I don't know how to predict whether a given person will benefit from it from the standpoint of the gut, or whether it will cause them excitotoxicity problems.

Deep thanks, as always, for your considered opinions and time.

***You're welcome. Sorry I can't give a more straightforward answer.

***Best regards,

***Rich
 

triffid113

Day of the Square Peg
Messages
831
Location
Michigan
I dont have time to read through this whole thread but just wanted to say that I have low HCL and yet no prob. with digesting protein and I think it is because I take Olive Leaf Extract and it keeps my gut free of pathogens (which is one of the jobs of HCL).

idk what it's worth but I will also report that I take a Triple Action Cruciferous Vegetable extract from Life Extension (from iherb) and so I get cysteine directly. I take it to ward off hormonal cancer for my bioidentical hormone replacement. I dont know what Fredd would have to say about it or how it relates to NAC. My hormones come out perfect with this supplement though so I am sold on it.

Take care
Trif